Capricor to Meet With FDA Following Positive 3-Year Data on Duchenne Agent CAP-1002

Linda Marbán, PhD

According to a recent announcement, Capricor Therapeutics announced it will host a pre-biologics license application (BLA) meeting with the FDA over the coming months to discuss options to expedite a BLA filing for its investigational agent CAP-1002 as a therapy for Duchenne muscular dystrophy (DMD). The decision comes as the company reported positive 3-year data from the open-label extension (OLE) of its phase 2 HOPE-2 trial (NCT03406780).¹

Following the completion of the double-blind, placebo-controlled portion of HOPE-2, eligible patients who wished to remain on treatment entered the OLE where they received CAP-1002, also known as deramiocel, at 150 million cells per infusion every 3 months. At 3 years from the start of the OLE study, patients with DMD on the active therapy (n = 12) showed a –4.1-point change in performance of upper limb (PUL v2.0), the primary end point, compared with changes of –7.8 for an external comparator (n = 32; delta change, +3.7 points; P <.001).

The external comparator PUL data was provided by Cincinnati Children’s Hospital Medical Center (CCHMC). Secondary outcomes, which comprised of 5-year data from the start of HOPE-2, showed a change of +1.2% in left ventricular ejection fraction (LVEF), an end point of cardiac function, for deramiocel-treated patients (n = 10). For those who had at least 45% LVEF at the end of HOPE-2 (n = 8), this subgroup experienced a percent improvement of +3.0%.

"The results of the open label study are tremendously important for DMD patients, as they showed sustained skeletal and cardiac benefits after 3 years of continuous treatment with deramiocel, which underscores the potential long-term benefits this therapy can offer patients with DMD,” Linda Marbán, PhD, chief executive officer at Capricor, said in a statement.¹ "Based on our HOPE-2 OLE data and prior clinical results, we plan to discuss with the FDA options to expedite our Biologics License Application (BLA) filing. We continue to work closely with FDA with the goal of bringing deramiocel to patients as quickly as possible and look forward to sharing further updates as they become available. We thank the patients, their families and the broader Duchenne community for continuing to work with us throughout the development of this promising therapy."

All cardiac outcomes were measured using MRI imaging. For the overall deramiocel population, investigators reported improvements of –2.4 mL/m2 and –5.7 mL/m2 for LV end systolic volume and LV end diastolic volume, respectively. Those in the subgroup of deramiocel-treated patients who had at least 45% LVEF at the end of HOPE-2 showed changes of –5.1 and –10.0, respectively. Of note, only 10 of the 12 participants in the study were able to receive MRI.

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HOPE-2, which enrolled originally 26 patients from 2018 to 2020, had original data published in The Lancet in 2022. In total, 8 patients were randomly assigned to CAP-1002 and 12 to placebo, with 6 not randomized due to screening failure. Overall, among those who had a post-treatment PUL 1.2 assessment, the mean 12-month change from baseline in mid-level elbow PUL1.2 favored CAP-1002 over placebo (percentile difference, 36.2%; 95% CI, 12.7-59.7; difference, 2.6 points; P = .014).²

CAP-1002 is the clinical formulation of human allogeneic cardiosphere-derived cells (CDCs). CDCs are a type of stromal or progenitor cell that has been shown in preclinical and clinical studies to exert immunomodulatory, antifibrotic, and regenerative actions in dystrophinopathy and heart failure. HOPE-2 was the first trial of intravenous CAP-1002 for any indication and the first trial with repeat sequential dosing of cells for a genetic illness.

In HOPE-2, CAP-1002 was considered well tolerated in severely affected patients with DMD, with the exception of hypersensitivity reactions. Implementation of a pretreatment procedure with glucocorticoids, an H1 blocker, and an H2 blocker succeeded in preventing serious allergic reactions. Notably, patients on the active therapy showed a marked decrease in creatine kinase (CK)-MB as a proportion of total CK over the course of the study, indicative of reduced cardiac muscle damage. The proportion of CK-MB isozyme at month 12 in the placebo group was increased compared with the CAP-1002 group (percentile difference, 29.1%; 95% CI, 4.0-54.2; P = .025).²

REFERENCES
1. Capricor Therapeutics announces long-term benefit of deramiocel (CAP-1002) in both skeletal muscle and cardiac function in the HOPE-2 OLE study in Duchenne muscular dystrophy. News release. June 28, 2024. Accessed July 8, 2024.
2. McDonald C, Marban E, Hendrix S, et al. Repeated intravenous cardiosphere-derived cell therapy in late-stage Duchenne muscular dystrophy (HOPE-2): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. The Lancet. 2022;399(10329):1049-1058. doi:10.1016/S0140-6736(22)00012-5.